Differences in Gene Expression Observed Between Risk-Taking and Risk-Avoiding Brains

Yonsei University and Catholic University Medical School Research Team
Analysis of Gene Expression Differences in the Medial Prefrontal Cortex Using Animal Models of Gambling Disorder

[Asia Economy Reporter Lee Gwan-ju] A study has found differences in gene expression in brain tissue depending on the temperament of 'risk preference,' such as risk-seeking or risk-avoidance.

The research team, including Professors Kim Jeong-hoon and Kim Hwa-young from the Department of Physiology at Yonsei University College of Medicine, researcher Kwak Myung-ji, and Professors Jeong Yeon-jun and Jeong Seung-hyun from the Department of Biomedical Science and Health at Catholic University College of Medicine, announced on the 16th that they discovered 477 genes expressed differently in the medial prefrontal cortex according to risk preference temperament.

Most addiction patients tend to take risks to obtain addictive substances even when negative outcomes are expected. This characteristic appears not only in drug addiction but also in behavioral addiction patients such as those with gambling disorder, showing difficulties in decision-making that determines risk preference.

It is known that genetic factors are involved in vulnerability to gambling disorder and risk-seeking behavior. However, most previous studies focused on single nucleotide polymorphisms (genetic variations showing a difference of one nucleotide in the sequence) through genome-wide association studies. This study is the first to deeply analyze the entire transcriptome expressed in specific brain tissues of individuals exhibiting such behaviors.

Gambling-type game animal model. When rewards and punishments are presented with different probabilities, risk-averse groups choose more advantageous options, while risk-seeking groups choose more disadvantageous options.

The research team separated experimental rats into a 'risk-avoidance group,' which chose options with small rewards per trial but ultimately gained more rewards over multiple trials, and a 'risk-seeking group,' which chose options with large rewards per trial but ultimately gained fewer rewards over multiple trials through gambling-like game training.

They isolated the medial prefrontal cortex and the septal nucleus accumbens from these rats' brains and analyzed the expression of all transcripts within. They found quantitative differences in the expression of 477 and 36 genes, respectively. Among these, they performed functional enrichment analysis (a method analyzing cellular mechanisms, functions, and signaling pathways involving specific genes) and protein interaction network analysis on genes whose expression levels were significantly lower in the medial prefrontal cortex of the risk-seeking group compared to the risk-avoidance group, selecting gene groups presumed to contribute to risk-seeking behavior.

Quantitative expression of 477 genes in the medial prefrontal cortex differed according to risk preference. Functional analysis and protein network analysis suggest that several genes, including the voltage-dependent calcium channel complex, are involved in risk-taking behavior.

The research team explained that this study is significant in identifying genes that actually show different expression in specific brain regions involved in decision-making according to risk choice behavior, and it is expected to help understand the genetic differences in decision-making disorders vulnerable to addiction diseases.

Professor Kim Jeong-hoon said, “Based on these results, we plan to conduct more in-depth research on the functional roles of specific genes involved in risk-choice behavior.” Professor Jeong Yeon-jun added, “We plan to separate cells by type and perform precise analysis of gene expression differences at the single-cell level in the future.”

The study results were published in the latest issue of the international journal of behavioral addiction, the Journal of Behavioral Addictions.

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